DNA methylation changes in biomarker loci occur early in cancer progression

Abstract

Tumor-specific DNA methylation can be used for cancer diagnostics and monitoring.  We have recently reported a set of DNA methylation biomarkers that can distinguish plasma samples from lung cancer patients versus healthy controls with high sensitivity and specificity.  Furthermore, the DNA methylation signal from the biomarker loci detected in plasma samples correlated with tumor size and decreased after surgical resection of lung tumors.  In order to determine the timing of DNA methylation of these loci during carcinogenesis and thus the potential of the biomarkers to detect early stages of the disease we analyzed the DNA methylation of the biomarker loci in five precancerous conditions using available data from the GEO database.  We found that the DNA methylation of the biomarker loci is gained early in carcinogenesis since most of the precancerous conditions already have biomarker loci hypermethylated.  Moreover, these DNA methylation biomarkers are able to distinguish between precancerous lesions with malignant potential and those that stay benign where data is available.  Taken together, the biomarkers have the potential to detect the earliest cancer stages; the only limitation to detection of cancer from plasma samples or other liquid biopsies is the timing when tumors start to shed enough DNA into body fluids.